Support-bound proteins are finding increasing utility, for example, in the search for small molecule modulators of the proteins in drug discovery programs. Recently, protein arrays have been described for high-throughput screening (see co-pending application Ser. No. 09/115,455, filed Jul. 14, 1998; Ser. No. 09/353,215, filed Jul. 14, 1999 and Ser. No. 09/353,555, filed Jul. 14, 1999; and related PCT published applications WO 00/04382, 00/04389 and 00/04390).
Applications Ser. Nos. 09/353,215 and 09/353,555 describe a number of hurdles that must be overcome to provide protein arrays of high quality which produce accurate and reproducible screening results. Typically, proteins must remain hydrated, be kept at ambient temperatures, and are very sensitive to the physical and chemical properties of the support materials. Thus, maintaining protein activity at the liquid-solid interface requires new immobilization strategies which address the sensitivity of the proteins to the environment and further can orient the protein in a manner which ensures accessibility of the protein active site to potentially interacting molecules.
The present invention addresses these and other considerations in the preparation and use of protein arrays.